A 419259 (Synonyms: RK-20449) |
Catalog No.GC35209
One-Click Copy Product Info
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A 419259 es un inhibidor de pirrolo-pirimidina de amplio espectro, diseÑado para mejorar la selectividad hacia la familia Src con IC50 de 9 nM, <3 nM y <3 nM para Src, Lck y Lyn, respectivamente.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 364042-47-7
Sample solution is provided at 25 µL, 10mM.
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A 419259 is a pyrrolopyrimidine Src family kinase inhibitor with IC50 values of 9nM, <3nM and <3nM for the Src family members Src, Lck and Lyn, respectively[1].
In vitro, A 419259 (0-1µM; 0-4d) blocked the proliferation and induced apoptosis of Ph⁺ leukemia cells (K-562 and Meg-01) in a dose-dependent manner, without markedly affecting Ph⁻ myeloid leukemia cells (TF-1 and HEL)[1]. A 419259 (1µM; 16h) inhibited Lck and c-Src activity in self-renewing H1 hES cells[2]. A 419259 (1µM; 24h) inhibited Src-related signaling, thereby affecting the differentiation of mouse embryonic stem cells (mESCs)[3].
In vivo, A 419259 (30mg/kg; i.p.; twice) inhibited HCK/NLRP3 inflammasome signaling, reduced IL-1β release and alleviated hepatic inflammation in LPS-induced mice[4]. A 419259 (0.5mg/kg; i.p.; once every three days for three times) reduced phosphorylated Src levels in the spinal cord and skeletal muscle, improved motor function and extended lifespan in AR-97Q transgenic male mice[5]. A 419259 (5mg/kg; i.v.; once) significantly inhibited tumor growth and reduced tumor weight in CD-1 mice bearing CAL51 tumors[6].
References:[1] Wilson MB, Schreiner SJ, Choi HJ, Kamens J, Smithgall TE. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene. 2002;21(53):8075-8088.
[2] Zhang X, Simerly C, Hartnett C, Schatten G, Smithgall TE. Src-family tyrosine kinase activities are essential for differentiation of human embryonic stem cells. Stem Cell Res. 2014;13(3 Pt A):379-389.
[3] Meyn MA 3rd, Smithgall TE. Chemical genetics identifies c-Src as an activator of primitive ectoderm formation in murine embryonic stem cells. Sci Signal. 2009;2(92):ra64.
[4] Kong X, Liao Y, Zhou L, et al. Hematopoietic Cell Kinase (HCK) Is Essential for NLRP3 Inflammasome Activation and Lipopolysaccharide-Induced Inflammatory Response In Vivo. Front Pharmacol. 2020;11:581011.
[5] Iida M, Sahashi K, Kondo N, et al. Src inhibition attenuates polyglutamine-mediated neuromuscular degeneration in spinal and bulbar muscular atrophy. Nat Commun. 2019;10(1):4262.
[6] Cheung A, Opzoomer J, Ilieva KM, et al. Anti-Folate Receptor Alpha-Directed Antibody Therapies Restrict the Growth of Triple-negative Breast Cancer. Clin Cancer Res. 2018;24(20):5098-5111.
| Cell experiment [1]: | |
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Cell lines |
K-562 and Meg-01 cell lines |
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Preparation Method |
104 cells were plated per well in 96-well plates for each day of a 4-day time course. Various concentrations of A 419259 or vehicle control were added to the wells (five wells per concentration per day) and the plates were incubated at 37℃. At each time point, one plate was centrifuged at 1500g for 10min to pellet the cells. Cells were washed with PBS, and calcein-AM was added to each well to a final concentration of 1mM. Plates were incubated in the dark at room temperature for 1h. The plates were then read at 485/530nm (excitation/emission) using a SpectraMax Gemini XS fluorescent plate reader and data were analysed with SoftMax Pro software |
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Reaction Conditions |
0-1µM; 0-4d |
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Applications |
A 419259 block Ph+ leukemia cell (K-562 and Meg-01) proliferation in a dose dependent fashion. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
C57BL/6 mice were injected intraperitoneally (i.p.) with 30mg/kg A 419259 or the vehicle control (DMSO/PBS) 24h and 12h before i.p. injection of 5mg/kg LPS or PBS. Mice were sacrificed after 3h, and the tissues were stored at −80°C and prepared for immunoblotting. |
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Dosage form |
30mg/kg; i.p.; twice |
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Applications |
Mice treated with A 419259 showed reduced response to LPS, with lower amounts of secreted IL-1β than in vehicle-treated mice. A 419259 could markedly decrease the inflammatory cells’ infiltration in the liver. The protein levels of NLRP3 and caspase 1 (P20) in the liver decreased when the mice were treated with A 419259. |
| References: [1] Wilson MB, Schreiner SJ, Choi HJ, Kamens J, Smithgall TE. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene. 2002;21(53):8075-8088. [2] Kong X, Liao Y, Zhou L, et al. Hematopoietic Cell Kinase (HCK) Is Essential for NLRP3 Inflammasome Activation and Lipopolysaccharide-Induced Inflammatory Response In Vivo. Front Pharmacol. 2020;11:581011. | |
| Cas No. | 364042-47-7 | SDF | |
| Sinónimos | RK-20449 | ||
| Canonical SMILES | NC1=C2C(N([C@H]3CC[C@H](N4CCN(C)CC4)CC3)C=C2C5=CC=C(OC6=CC=CC=C6)C=C5)=NC=N1 | ||
| Formula | C29H34N6O | M.Wt | 482.62 |
| Solubility | 55 mg/mL in water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.072 mL | 10.3601 mL | 20.7202 mL |
| 5 mM | 414.4 μL | 2.072 mL | 4.144 mL |
| 10 mM | 207.2 μL | 1.036 mL | 2.072 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)